Central nervous system (CNS) disorders are economically and socially devastating. For example, schizophrenia is one of the leading causes of disability worldwide with a lifetime prevalence of 0.6 to 1.3% of the population characterized by high morbidity and mortality. Less than 15% of people with this disability are competitively employed, while about 20% live independently.
Schizophrenia is generally characterized by positive symptoms (such as delusions, hallucinations, and disorganized behavior), negative symptoms (such as anergia), affective symptoms (such as dysphoria, hopelessness, anxiety, hostility, aggression) and/or cognitive deficits.
Typical treatments for such disorders include drugs that affect the monoamine receptor systems. For example, the primary effect of first generation antipsychotics is dopamine (D2 receptor) blockade. While these are effective in treating the positive symptoms of schizophrenia, they exert only modest effects on negative symptoms and cognitive deficits.
Thus, despite the availability of some drugs for treating CNS disorders such as schizophrenia, there is an unmet need for improved methods and compounds for treating central nervous system disorders.